The Aim is to develop a new instrument that uniquely senses small specific intermolecular interactions. This Bioprobe Force Microscope (BFM) utilizes functionalized biospecific tips and modified atomic force microscopy controller functions. Initial studies strongly suggest we can measure binding forces between adrenoreceptors (BAR), a biomedically important receptor, and an beta-antagonist drug. The Specific Aims of Phase I are to: (1) confirm that we are measuring specific binding forces between receptors and ligands, and (2) functionalize the tip with differing mixtures of receptor/lipid to relate binding forces to receptor density. Phase II will investigate in detail tip characteristics and different receptor tips and perhaps coatings for other purposes; develop software and controller functions; and apply the BFM to real problems in pharmacology and other living science. At the end of the Phase II, we hope to have developed a BFM and various tips which have been demonstrated in a variety of systems to quantitatively study drug/ligand interactions. This would represent the end of the initial stages of basic research. The initial products could then be developed into commercial products as well as into services that ultimately will support a wide variety of investigations. What we have learned should be generalizable to a whole universe of applications in which it is important to have information on the interaction between molecules. PROPOSED COMMERCIAL APPLICATION The BFM should represent a major break- through for investigators in biological, biochemical, biomedical cellular and molecular biologic, medical, pharmacologic including combinatorial chemistry, physiologic, virologic and virtually all living sciences because of its sensitivity in force measurement, high resolution, extremely small sample requirements, and ability to operate in a physiologic environment. The principles will also be useful to the studies of solids, gases and liquids in physics, chemistry, geochemistry and other fields in which nanoscale charge resolution is useful.